Immature renal structures associated with a novel UMOD sequence variant.
Mutations of the UMOD gene, encoding uromodulin, have been associated with medullary cystic kidney disease 2, familial juvenile hyperuricemic nephropathy, and glomerulocystic kidney disease. We report on a 13-year-old boy presenting with chronic reduced kidney function, hyperuricemia, and impairment in urine-concentrating ability. His father was affected by an undefined nephropathy that required transplantation. The boy's renal ultrasonography showed reduced bilateral kidney volumes and cortical hyperechogenicity, with 2 tiny cysts in the left kidney. Renal biopsy showed up to 60% of glomeruli featuring an enlargement of Bowman space (glomerular cysts), with mild interstitial fibrosis (alpha-smooth muscle actin [alphaSMA] positive), inflammatory infiltrate, and focal tubular atrophy at the cortical level. At the corticomedullary junction, immature tubules (some dilated) with cytokeratin- and paired box gene 2 (PAX2)-positive immunostaining were seen, surrounded by vimentin-positive mesenchymal tissue. Unlike previously reported cases, no uromodulin-positive globular aggregates within the cytoplasm of tubular cells were observed. Uromodulin urinary excretion was absent. Genetic analysis showed a novel heterozygous sequence change in the UMOD gene (NM_003361.2:c.149G-->C; p.Cys50Ser) involving the first epidermal growth factor-like domain of the protein in both the boy and his father. This novel UMOD sequence variant, which is associated with an immunohistochemical pattern different from previous reports and a histological picture characterized by immature renal structures, suggests a possible role for UMOD in renal development.
Benetti
Elisa
E
Pediatric Nephrology, Dialysis, and Transplantation Unit, Department of Pediatrics, University of Padua, Padova, Italy. elisabene@libero.it
Caridi
Gianluca
G
Vella
Manuela Della
MD
Rampoldi
Luca
L
Ghiggeri
Gian Marco
GM
Artifoni
Lina
L
Murer
Luisa
L
D000293:Adolescent; D019943:Amino Acid Substitution; D006801:Humans; D007672:Kidney Cortex / Q000473:pathology; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000473:pathology; D007679:Kidney Medulla / Q000473:pathology; D008297:Male; D009088:Mucoproteins / Q000235:genetics*; D020125:Mutation, Missense; D058949:Uromodulin
D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin